RT Journal Article
SR Electronic
T1 Onset of differentiation is posttranscriptionally controlled in adult neural stem cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 289868
DO 10.1101/289868
A1 Avni Baser
A1 Yonglong Dang
A1 Maxim Skabkin
A1 Gülce S. Gülcüler Balta
A1 Georgios Kalamakis
A1 Susanne Kleber
A1 Manuel Göpferich
A1 Roman Schefzik
A1 Alejandro Santos Lopez
A1 Enric Llorens Bobadilla
A1 Carsten Schultz
A1 Bernd Fischer
A1 Ana Martin-Villalba
YR 2018
UL http://biorxiv.org/content/early/2018/03/27/289868.abstract
AB The contribution of posttranscriptional regulation of gene expression to neural stem cell differentiation during tissue homeostasis remains elusive. Here we show highly dynamic changes in protein synthesis along differentiation of stem cells to neurons in vivo. Examination of individual transcripts using RiboTag mouse models reveals that neural stem cells efficiently translate abundant transcripts, whereas translation becomes increasingly controlled with the onset of differentiation. Stem cell generation of early neuroblasts involves translational repression of a subset of mRNAs including the stem cell-identity factors Sox2 and Pax6 as well as translation machinery components. In silico motif analysis identifies a pyrimidine-rich motif (PRM) in this repressed subset. A drop in mTORC1 activity at the onset of differentiation selectively blocks translation of PRM-containing transcripts. Our data uncovers how a drop in mTORC1 allows robust simultaneous posttranscriptional repression of key stem cell identity-factors and translation-components and thereby stemness exit and migration.